Chapter 4 Principles of Neural and Hormonal Communication

Chapter 4Principles of Neural and

Hormonal Communication

• Write and answer detailed questions about how membrane potentials are propagated, converted to chemical signals (neurotransmitters) at synapses, and create postsynaptic potentials. This will be measured by exams, quizzes and student generated questions in class discussions.

Outline• Graded Potentials• Action Potentials• Synapses and integration• Intracellular communication• Signal Transduction• Hormonal Communication• Nervous vs. Endocrine System

Communication is critical for the survival of the cells that compose the body.

Two major regulatory systems of the body – nervous and endocrine - communicate with the cells/tissues/organs/systems they control.

Neural communicationHormonal communication

Neural Communication• Nerve and muscle cells are excitable tissues. • Can alter their membrane permeabilities.• Permeability changes lead to membrane

potential changes. • Potential changes act as electrical signals. • Electrical signals are necessary for normal nerve

and muscle function.

Time (msec)

Mem

bra

ne

po

ten

tial

(m

V)

Hyperpolarization (increase inpotential; membrane more negative)

Depolarization (decrease in potential;membrane less negative)

Repolarization (return to resting potentialafter depolarization)

Resting potential

–90–80–70

–60–50–40–30–20–10

0+10+20

Fig. 4-1, p. 90

• Membrane electrical states– Polarization

• Any state when the membrane potential is other than 0mV– Depolarization

• Membrane becomes less polarized than at resting potential– Repolarization

• Membrane returns to resting potential after having been depolarized– Hyperpolarization

• Membrane becomes more polarized than at resting potential

Neural Communication

Voltage clamp • The technique allows an experimenter to "clamp" the cell potential at a chosen value.

• This makes it possible to measure how much ionic current crosses a cell's membrane at any given voltage.

• This is important because many of the ion channels in the membrane of a neuron are voltage gated ion channels, which open only when the membrane voltage is within a certain range.

Kenneth Cole[2] and George Marmount

https://www.youtube.com/watch?v=Wd_gKJoo25Y

Patch clamp• A patch-clamp microelectrode is a micropipette with a relatively large tip diameter. • The microelectrode is placed next to a cell, and gentle suction is applied through the

microelectrode to draw a piece of the cell membrane (the 'patch') into the microelectrode tip; the glass tip forms a high resistance 'seal' with the cell membrane.

• This can be used for studying the activity of the ion channels that are present in the patch of membrane.

• If more suction is now applied, the small patch of membrane in the electrode tip can be displaced, leaving the electrode sealed to the rest of the cell.

• This "whole-cell" mode allows very stable intracellular recording.

This technique was developed by Erwin Neher and Bert Sakmann who received the Nobel Prize in 1991.

https://www.youtube.com/watch?v=8LDO0hWWc0Q

Channels• Leak channels

– Unregulated passage of ions• Gated channels

– Voltage gated– Chemically gated– Mechanically gated– Thermally gated

• These channels create and alter membrane potentials• Two kinds of potential change

– Graded potentials• Serve as short-distance signals

– Action potentials• Serve as long-distance signals

Graded Potential• Occurs in small, specialized region of excitable cell

membranes • Magnitude of graded potential varies directly with the

magnitude of the triggering event• Die out over short distances

Fig. 4-2, p. 87

Current Flow During a Graded Potential

Graded Potentials

Examples of graded potentials:• Postsynaptic potentials• Receptor potentials• End-plate potentials• Pacemaker potentials• Slow-wave potentials

Action Potentials• Brief, rapid, large (100mV) changes in

membrane potential during which potential actually reverses

• Involves only a small portion of the total excitable cell membrane

• Do not decrease in strength as they travel from their site of initiation throughout remainder of cell membrane

Time (msec)

Slow depolarizationto threshold

1 msec

After hyperpolarization

Resting potential

Threshold potential

Action potential

Mem

bra

ne

po

ten

tial

(m

V)

+70

0

–90

–80

–70–60

–50–40–3020

–10

+10+20+30

+40+50

+60

Fig. 4-4, p. 94

(e) Open

Delayedopeningtriggeredat threshold

Activationgate

VOLTAGE-GATED POTASSIUM CHANNEL

(c) Closed and notcapable of opening(inactivated)

Rapidopeningtriggeredat threshold

(a) Closed butcapable of opening

Inactivation gate

Activation gateICF

Plasmamembrane

ECF

(d) Closed

Slowclosingtriggeredat threshold

(b) Open(activated)

VOLTAGE-GATED SODIUM CHANNEL

Fig. 4-5, p. 95

ANIMATION: Action Potential

Action Potentials

• When membrane reaches threshold potential – (-50 to-55mv)

– Voltage-gated channels in the membrane undergo conformational changes

– Flow of sodium ions into the ICF reverses the membrane potential from -70 mV to +30 mV

– Flow of potassium ions into the ECF restores the membrane potential to the resting state

Action Potentials• Additional characteristics

– Sodium channels open during depolarization by positive feedback.

– When the sodium channels become inactive, the channels for potassium open. This repolarizes the membrane.

– As the action potential develops at one point in the plasma membrane, it regenerates an identical action potential at the next point in the membrane.

– Therefore, it travels along the plasma membrane undiminished.

Fig. 4-7a, p. 96

Na+ channel closes and is inactivated(activation gate still open; inactivationgate closes)

Na+ channelopens andis activated(activationgate opens;inactivationgate alreadyopen)

K+ channel opens(activation gate opens)

K+ voltage-gated channel closed(activation gate closed)

Me

mb

ran

e p

ote

nti

al

(mV

)

Na+ voltage-gated channel closed(activation gate closed; inactivation gate open)

Time (msec)

Depolarizingtriggering event

Resting potential

Threshold potential

K+ channelcloses(activationgate closes)

Na+ channelreset to closedbut capableof opening(activationgate closes;inactivationgate opens)

K+ o

ut →

falling

ph

ase

Na

+ in

→ r

isin

g p

has

e

ICF

ECF

11

22

33

44

55

66

77

88

Action Potentials

The Na+/K+ pump gradually restores the concentration gradients disrupted by action potentials.

• Sodium is pumped into the ECF• Potassium is pumped into the ICF• Refractory period keeps the action potential going in one

direction and limits the Ap frequency• All or none• Frequency and line coding

Table 4-1 p101

Action Potentials• The Na+–K+ pump gradually restores the ions

that moved during the action potential.• After an impulse has occurred in a patch of

membrane, the membrane enters its refractory period.

• It is impossible to re-stimulate the patch of membrane until it has recovered from its refractory period.

Refractory Periods• Absolute refractory period- period of time

when a patch of membrane cannot be re-stimulated no matter how strong the stimulus.

• Relative refractory period- period of time during which a patch of membrane can only be re-stimulated by a stronger than normal stimulus.

• Refractory periods ensure the one-way propagation of action potentials.

Fig. 4-10, p. 101

“Backward” currentflow does not reexcitepreviously active areabecause this area isin its refractory period

Direction of propagationof action potential

“Forward” current flow excitesnew inactive area

New adjacent inactive areainto which depolarizationis spreading; will soon reachthreshold

New active areaat peak of actionpotential

Previous activearea returned toresting potential

Neuron• Once initiated, action potentials are conducted

throughout a nerve fiber• Action potentials are propagated from the axon

hillock to the axon terminals• Basic parts of neuron (nerve cell)

– Cell body

– Dendrites

– Axon

Neuron

Neuron• Cell body

– Houses the nucleus and organelles

• Dendrites – Project from cell body and increase surface area

available for receiving signals from other nerve cells

– Signal toward the cell body

Dendrite and cell body serve as the neurons input zone.

Neuron• Axon

– Nerve fiber– Single, elongated tubular extension that conducts action

potentials away from the cell body– Conducting zone of the neuron– Collaterals

• Side branches of axon

– Axon hillock• First portion of the axon plus the region of the cell body fro m

which the axon leaves• Neuron’s trigger zone

– Axon terminals• Release chemical messengers that simultaneously influence

other cells with which they come into close association• Output zone of the neuron

Action Potentials

• Two types of propagation– Contiguous conduction

• Conduction in unmyelinated fibers

• Action potential spreads along every portion of the membrane

– Saltatory conduction • Rapid conduction in myelinated fibers

• Impulse jumps over sections of the fiber covered with insulating myelin

Fig. 4-9b, p. 100

Remainder of axonstill at resting potential

New adjacentinactive area into which depolarization is spreading; will soon reach threshold

Adjacent area that was brought tothreshold by local current flow; nowactive at peak of action potential

Previous activearea returnedto restingpotential; nolonger active; inrefractory period

Contiguous Conduction

Fig. 4-9a, p. 100

Direction of propagation of action potential

Gradedpotential> threshold

Local current flow that depolarizesadjacent inactive area from restingpotential to threshold potential

Remainder of axonstill at resting potential

Adjacent inactive area into which depolarization is spreading; will soon reach threshold

Active area atpeak of actionpotential

Contiguous Conduction

Fig. 4-12a, p. 103(a) Myelinated fiber

Plasmamembrane

Axon of neuron

Nodes of Ranvier Myelin sheath

Myelinsheath

Axon

Saltatory Conduction

Fig. 4-12d, p. 103

Node ofRanvier

Axon

Voltage-gatedNa+ and K+channels

Myelinsheath

Saltatory Conduction• Propagates action potential faster than

contiguous conduction because action potential does not have to be regenerated at myelinated section

• Myelinated fibers conduct impulses about 50 times faster than unmyelinated fibers of comparable size

• Myelin – Primarily composed of lipids

– Formed by oligodendrocytes in CNS

– Formed by Schwann cells in PNS

Direction of propagationof action potential

Adjacent inactive nodeinto which depolarizationis spreading; will soonreach threshold

Remainder of nodesstill at resting potential

Active node at peakof action potential

Local current flow thatdepolarizes adjacent inactivenode from resting to threshold

Fig. 4-13, p. 104

Regeneration of Nerve Fibers• Regeneration of nerve fibers depends on its

location• Schwann cells in PNS guide the regeneration of

cut axons• Fibers in CNS myelinated by oligodendrocytes

do not have regenerative ability– Oligodendrocytes inhibit regeneration of cut

central axons

Synapses• Junction between two neurons• Primary means by which one neuron directly interacts

with another neuron (muscle cells or glands as well)• Anatomy of a synapse

– Presynaptic neuron – conducts action potential toward synapse

– Synaptic knob – contains synaptic vesicles

– Synaptic vesicles – stores neurotransmitter (carries signal across a synapse)

– Postsynaptic neuron – neuron whose action potentials are propagated away from the synapse

– Synaptic cleft – space between the presynaptic and postsynaptic neurons

Synaptic knob(presynapticaxon terminal)

Chemically gatedreceptor-channelfor Na+, K+, or Cl–

Neuro-transmittermolecule

Voltage-gatedCa2+ channel Ca2+

Postsynaptic neuron

Subsynapticmembrane

Synapticcleft

Synapticvesicle

Axon ofpresynapticneuron

Receptor forneurotransmitter

1

2

3

4

5

3

4

5

Fig. 4-15, p. 108

Axon terminalof presynapticneuron

Synapticvesicles

Synapticcleft

Dendrite ofpostsynapticneuron

Fig. 4-15, p. 108

Neurotransmitters• Vary from synapse to synapse• Same neurotransmitter is always released at a particular

synapse• Quickly removed from the synaptic cleft

SynapsesSignal at synapse either excites or inhibits the postsynaptic

neuron• Two types of synapses

– Excitatory synapses– Inhibitory synapses

• If binding of NT opens Na+ and K+ channels the result is a small depolarization called an excitatory post-synaptic potential (EPSP).

• EPSP brings the cell closer to threshold. • If binding of NT opens either K+ or Cl– channels the result

is a small hyperpolarization called an inhibitory post-synaptic potential (IPSP).

• IPSP means cell less likely to reach threshold.

Cell body of postsynapticneuron

Axon hillock

Synaptic Summation

• Multiple EPSP and IPSP’s from numerous synapses converge on one neuron.

• These signals can cause different changes in the postsynaptic neuron– Cancellation

– Spatial summation

– Temporal summation

Synaptic Summation

Inhibitorypresynaptic input

Postsynapticcell

Excitatorypresynaptic inputs

Membranepotentialrecorded

Po

sts

yn

ap

tic

me

mb

ran

e p

ote

nti

al

(mV

)

ThresholdpotentialRestingpotential

(d) EPSP-IPSPcancellation

Time (msec)

–70

(a) Nosummation

(b) Temporalsummation

(c) Spatialsummation

+30

0–50

Fig. 4-17, p. 111

Fig. 4-19, p. 109

Presynapticinputs

Postsynapticneuron

Convergence of input(one cell is influencedby many others)

Presynapticinputs

Divergence of output(one cell influencesmany others)

Postsynapticneurons

Arrows indicate direction in which information is being conveyed. Fig. 4-20, p. 111

Synaptic Drug Interactions• Possible drug actions

– Altering the synthesis, axonal transport, storage, or release of a neurotransmitter

– Modifying neurotransmitter interaction with the postsynaptic receptor

– Influencing neurotransmitter reuptake or destruction

– Replacing a deficient neurotransmitter with a substitute transmitter

Examples of drugs that alter synaptic transmission• Cocaine

– Blocks reuptake of neurotransmitter dopamine at presynaptic terminals

• Strychnine– Competes with inhibitory neurotransmitter glycine

at postsynaptic receptor site

• Tetanus toxin– Prevents release of inhibitory neurotransmitter

GABA, affecting skeletal muscles

(a) Gap junctions

Small molecules and ions

(b) Transient direct linkup of cells’ surface markers

(c) Paracrine secretion

Local target cell

Paracrine

Secreting cell

Neurotransmitter(d) Neurotransmitter secretion

Secreting cell(neuron)

Electrical signal

Local target cell

(e) Hormonal secretion

Nontarget cell(no receptors)

Distant target cell

Hormone

Secreting cell(endocrine cell)

Blood

Distant target cell

Nontarget cell(no receptors)

Secreting cell(neuron)

Electrical signal

Neurohormone Blood

DIRECT INTERCELLULAR COMMUNICATION

INDIRECT INTERCELLULAR COMMUNICATION VIA EXTRACELLULAR CHEMICAL MESSENGERS

(f) Neurohormone secretionFig. 4-20, p. 117

Chemical Messengers

Four types:• paracrines (local chemical messengers) • neurotransmitters (very short-range chemical messengers released by neurons)

• hormones (long-range chemical messengers secreted into the blood by endocrine glands)

• neurohormones (long-range chemical messengers secreted into blood by neurons)

Hormones• Endocrinology

– Study of homeostatic activities accomplished by hormones

• Two distinct groups of hormones based on their solubility properties– Hydrophilic hormones (Proteins, peptides)

• Highly water soluble

• Low lipid solubility

– Lipophilic hormones (Steroids)• High lipid solubility

• Poorly soluble in water

Chemical Messengers• Extracellular chemical messengers bring about

cell responses primarily by signal transduction– Process by which incoming signals are conveyed

to target cell’s interior• Binding of extracellular messenger (first

messenger) to matching receptor brings about desired intracellular response by either– Opening or closing channels– Activating second-messenger systems

• Activated by first messenger• Relays message to intracellular proteins that carry out

dictated response

Fig. 4-23, p. 116

Fig. 4-24, p. 118

Fig. 4-25, p. 119

ANIMATION: Signal Transduction

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ANIMATION: Response Pathways Activated by G-Protein-Coupled Receptors

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Nucleus

Hormoneresponseelement

Gene

DNA

mRNA

Newprotein

Cellular response

DNA-bindingsite (active)

Portionthat bindshormone

Steroidhormone

Plasmaproteincarrier

Blood vessel

Steroidhormonereceptor Portion

that bindsto DNA

ECF

Cytoplasm

PlasmamembranePlasmamembrane

1

2

3

4

6

9

8

7

5

Fig. 4-28, p. 128

Comparison of Nervous System and Endocrine System